Treatment Of Retinoblastoma Research Articles

Bioactive Polymeric Nanoparticles of Moringa oleifera Induced Phyto-Photothermal Sensitization for the Enhanced Therapy of Retinoblastoma

Treatment of retinoblastoma is limited due to its delayed detection and inaccesbility of drugs to reach the retina crossing the blood-retinal barrier. With the advancements in nanotechnology, photothermal therapy (PTT) employing plasmonic nanomaterials and/or NIR dyes have emerged as an affordable alternative owing to the spatial control that is offered by the modality leading to localized and enhanced therapeutic efficacy with minimal invasiveness. However, the modality is limited in its clinical application owing to the increased heat shock resistance of the tumor cells in response to the heat that is generated via PTT. Hence, in this study, we explore the role of novel biomolecular fraction of Moringa oleifera (DFM) encapsulated within a polymeric nanosystem, for its anti-heat shock protein (HSP) activity. The MO extract was co-encapsulated with NIR sensitizing dye, IR820 into a biodegradable polycaprolactone (PCL) nano-delivery system (PMIR NPs). The photothermal transduction efficacy of PMIR NPs was validated in vitro against retinoblastoma cell lines. The inherent fluorescence of DFM was utilized to evaluate the cellular internalization of the PMIR NPs using fluorescence microscopy and flow cytometry. The overall oxidative protein damage and downregulation of HSP70 expression upon treatment with PMIR NPs and NIR laser irradiation was evaluated using densiometric protein analysis and Western blotting. Overall, the PMIR NPs exhibited excellent anti-cancer activity when combined with PTT with downregulated HSP70 expression against retinoblastoma cells.

MDM2 promotes cancer cell survival through regulating the expression of HIF-1α and pVHL in retinoblastoma.

Hypoxia is an important tumor feature and hypoxia-inducible factor 1 (HIF-1) is a master regulator of cell response to hypoxia. Mouse double minute 2 homolog (MDM2) promotes cancer cell survival in retinoblastoma (RB), with the underlying mechanism remaining elusive. In this study, we investigated the role of MDM2 and its relation to HIF-1α in RB. Expression analysis on primary human RB samples showed that MDM2 expression was positively correlated with that of HIF-1α while negatively correlated with von Hippel-Lindau protein (pVHL), the regulator of HIF-1α. In agreement, RB cells with MDM2 overexpression showed increased expression of HIF-1α and decreased expression of pVHL, while cells with MDM2 siRNA knockdown or MDM2-specific inhibitor showed the opposite effect under hypoxia. Further immuno-precipitation analysis revealed that MDM2 could directly interact with pVHL and promotes its ubiquitination and degradation, which consequently led to the increase of HIF-1α. Inhibition of MDM2 and/or HIF-1α with specific inhibitors induced RB cell death and decreased the stem cell properties of primary RB cells. Taken together, our study has shown that MDM2 promotes RB survival through regulating the expression of pVHL and HIF-1α, and targeting MDM2 and/or HIF-1α represents a potential effective approach for RB treatment.

The Predilection to Age, Sex, Laterally and Treatment of Retinoblastoma: A Retrospective Study at a Tertiary Eye Care Center in Bangladesh

The Predilection to Age, Sex, Laterally and Treatment of Retinoblastoma: A Retrospective Study at a Tertiary Eye Care Center in Bangladesh

Retinoblastoma: Current Management

Abstract Retinoblastoma (RB) is the most common intraocular malignancy in children. Unfortunately, survival in developing countries was found to be significantly worse (40%) compared with developed countries (79%). Early diagnosis and suspicion of RB in early intraocular stages is paramount for successful management and improved outcomes. The management of RB is in constant evolution for the sake of globe salvage. Treatment protocols are extremely diverse; varying from one case to another and are dependent on local resources, therefore, the success rates are variable. The introduction of chemotherapy in the early 1990s, especially intraarterial chemotherapy has led to remarkable success in treating eyes with more advanced diseases. Novel drugs, oncolytic viruses, and immunotherapy are promising approaches in the treatment of intraocular RB. This review navigates the landscape of RB management, delving into staging, diverse recent treatment modalities with their common side effects, and the ongoing challenges that necessitate a comprehensive approach.

Role of circular RNAs in retinoblastoma.

Retinoblastoma (RB), the most common malignant retinal tumor among children under 3years old, is lethal if left untreated. Early diagnosis, together with timely and effective treatment, is important to improve retinoblastoma-related outcomes. Circular RNAs (circRNAs), a new class of non-coding RNAs with the capacity to regulate cellular activities, have great potential in retinoblastoma diagnosis and treatment. Recent studies have identified circular RNAs that regulate multiple cellular processes involved in retinoblastoma, including cell viability, proliferation, apoptosis, autophagy, migration, and invasion. Six circular RNAs (circ-FAM158A, circ-DHDDS, circ-E2F3, circ-TRHDE, circ-E2F5, and circ-RNF20) promote disease progression and metastasis in retinoblastoma and function as oncogenic factors. Other circular RNAs, such as circ-TET1, circ-SHPRH, circ-MKLN1, and circ-CUL2, play tumor suppressive roles in retinoblastoma. At present, the studies on the regulatory mechanism of circular RNAs in retinoblastoma are not very clear. The purpose of this review is to summarize recent studies on the functional roles and molecular mechanisms of circular RNAs in retinoblastoma and highlight novel strategies for retinoblastoma diagnosis, prognosis, and treatment.

Twenty-Year Retrospective Study of Post-Enucleation Chemotherapy in High-Risk Patients with Unilateral Retinoblastoma.

Primary enucleation is a life-saving treatment for advanced intraocular retinoblastoma, particularly in patients with poor visual potential and functional contralateral eyes. This single-center study presents the treatment outcomes of patients with unilateral retinoblastoma who received primary enucleation and adjuvant chemotherapy with cyclophosphamide, vincristine, doxorubicin, and intrathecal methotrexate (CVDM) between 2000 and 2020. Twenty patients were enrolled in the study. The median age at diagnosis was 26 months (range, 1-45). Eighteen patients (90%) were in group E and two (10%) were in group D, according to the intraocular classification of retinoblastoma guidelines. Excluding one patient with an inadequate specimen, 19 patients (95%) had optic nerve involvement (ONI) at least up to the lamina cribrosa. Eight patients (40%) had choroidal invasion in addition to ONI. Two patients (10%) were surgical resection margin positive. The overall and event-free survival rates were 100% and 95%, respectively, for a median follow-up duration of 102.24 months (range 24.2-202.9). There were no relapses or deaths due to any cause, but one patient developed secondary rhabdomyosarcoma 99.6 months after chemotherapy. Treatment was well tolerated, with minimal hematotoxicity and hepatotoxicity. CVDM as a post-enucleation chemotherapy for advanced intraocular retinoblastoma has excellent outcomes with tolerable toxicity. However, in line with updated treatment trends, further risk stratification and lowering the treatment intensity should be considered. Continued long-term follow-up is required to further determine late effects.

Overview of Bilateral Retinoblastoma at Dr. M. Djamil General Hospital, Padang, Indonesia

Background: Retinoblastoma is the most common intraocular primary malignant tumor in children. In the United States, cases of retinoblastoma are estimated to be found in 1 in 18,000 children under 5 years. The incidence of retinoblastoma ranges from 1:14.00 to 1:34.000 live births. The highest incidence occurs in developing countries. This study aimed to provide a clinical picture of bilateral retinoblastoma at Dr. M. Djamil General Hospital, Padang, Indonesia, as basic data for further policy-making in order to optimize services related to the management of bilateral retinoblastoma.
 Methods: This study was a descriptive observational study with 29 study subjects. Sociodemographic, clinical, and management data are presented descriptively. Data analysis was performed with the help of SPSS software version 25.
 Results: Based on the age group, the majority of bilateral retinoblastoma cases were less than 5 years old, with the most age range being 3-4 years. The majority of therapeutic management for cases of bilateral retinoblastoma is exenteration in combination with chemotherapy.
 Conclusion: A combination of surgery and chemotherapy is the most frequently used treatment for bilateral retinoblastoma at Dr. M. Djamil General Hospital, Padang, Indonesia.

Impact of resveratrol-containing peptide nanospheres on retinoblastoma cells

For exploring an effective treatment of retinoblastoma (Rb), which is a threat to children, we constructed Resveratrol-peptide nanospheres (RES-PN) drug delivery system. Y-79 and S0-Rb50 cells were cultured to test the antitumor ability of RES-PN nanocomposites. In physicochemical properties test, we found PN could prolong RES half-life by about 3 times, and the particle size of RES-PN was about 214.10±3.73 nm, which was higher than that of PN (201.85±3.41 nm). Meanwhile, the encapsulation efficiency and drug loading rate of RES-PN were 90.77±3.51% and 9.82±0.64%, respectively. In the cell test, we found that RES-PN could better kill Rb cells and reduce their viability and invasiveness. Meanwhile, RES may induce Rb cell apoptosis through a mechanism possibly related to the JAK2/STAT3 axis. Hence, RES-PN shows great potential in Rb therapy.

MicroRNA-708 suppresses the proliferation, migration, and invasion of human retinoblastoma cells by targeting RAP2B, a member of the RAS oncogene family.

Retinoblastoma generally affects children and causes permanent vision failure or even death. MicroRNAs (miRs) have recently gained much attention during recent years. The miR-708 acts as a tumor suppressor in several human cancers, but the former has not been functionally characterized in human retinoblastoma. The present study was designed to investigate the role of miR-708 in human retinoblastoma. The results showed that miR-708 is significantly (P<0.05) downregulated in retinoblastoma cell lines. MiR-708 overexpression significantly (P<0.05) inhibited retinoblastoma cell growth and proliferation by inducing apoptosis. Furthermore, retinoblastoma cells overexpressing miR-708 exhibited a markedly lower migratory rate and invasiveness compared to negative control cells. The bioinformatics and dual luciferase assay revealed a RAS oncogene family protein, RAP2B, which acts as the regulatory target and functional mediator of the molecular role of miR-708 in retinoblastoma. Together, the present study revealed the tumor suppressor role of miR-708 and pointed to the therapeutic implications of miR-708/RAP2B in the treatment of retinoblastoma.

Preparation, Characterization and Antiradical Activity of Zinc Oxide Nanoparticles

Zinc oxide nanoparticles (ZnO NPs) have recently been studied as a multi-functional and multi-target nanomedicine for cancer treatment. They can be used not only as a nanocarrier for delivery of the chemotherapy drug but also as an antiradical agent due to their photo-catalytic and photo-oxidizing abilities. Our previous work showed a potential use of commercial-available ZnO NPs without and with carboplatin for the treatment of retinoblastoma. The aim of this work was to synthesize ZnO NPs having smaller particle size than the commercial ones, i.e., 100 nm average diameter, in order to improve the reaction time. ZnO NPs were prepared by a sol-gel technique and calcined with different calcination conditions. The structure and particle size of ZnO powders were characterized using an x-ray diffractometer and a particle size analyzer. Average nanoparticle sizes of 16.32 ± 1.64 nm were achieved at a calcination temperature of 300 degree Celsius and 1 hour holding time. The antiradical activity of prepared ZnO NPs in cooperation with ultraviolet irradiation was assessed using a putative model of cancer cells, i.e., 2,2(diphenyl-1-picryhydrazyl) radicals (DPPH*). An optical spectroscopy was used to detect the decrease in peak absorbance of the antiradical solution at a wavelength of 515 nm, which in turn can be used to calculate the percent remaining of DPPH*. The disappearance of DPPH* with respect to the reaction time revealed that prepared ZnO NPs (16.32 ± 1.64 nm) improved response time as compared with ZnO NPs (100 nm). Moreover, the effective ZnO concentrations to reduce the initial DPPH* concentration by 50%, also known as the EC50 value in the present study, is lower indicating the improvement of anti-proliferative activity when compared to the commercial ZnO NPs.

Phase-changeable nanoparticles loaded with FeⅢ-tannic acid/paclitaxel for retinoblastoma treatment

In this study, phase-changeable nanoparticles consisting of poly(lactic-co-glycolic acid) (PLGA) shells with FeⅢ-tannic acid (FeⅢTA), paclitaxel (PTX), and perfluorinated pentane (PFP) were prepared, and their therapeutic effect on retinoblastoma (RB) was evaluated. The killing effect of the FeⅢTA/PLGA/PTX/PFP (FPTP) + laser (FPTP + laser) treatment on Y79 cells was stronger than that of the blank control, laser, and FPTP treatments. Moreover, this effect increased with increasing concentration. In vivo experiments showed that the nanoparticles clustered at the tumor sites in mice and that laser excitation produced heat. The tumor volume increased gradually over time in the blank control and laser groups but not in the PTX, PLGA/PTX/PFP + laser, and FPTP groups. The FPTP + laser group showed the best tumor-volume-reduction results. The results collectively suggest that FPTP nanoparticles have good therapeutic effects on RB and may potentially be applied as a new integrated approach for RB diagnosis and treatment.

Intravitreal Carboplatin as Salvage Treatment for Progressive Vitreous Disease in Retinoblastoma: A Phase I Clinical Trial

To determine the safety and toxicity profile of intravitreal carboplatin as salvage treatment for retinoblastoma with vitreous disease. Single-institution, interventional prospective clinical trial. Patients with progressive or recurrent vitreous seeds after completion of primary treatment for intraocular retinoblastoma. Eligible eyes received an intravitreal injection of carboplatin every 14 to 21 days with simultaneous focal therapy (laser, thermotherapy, and brachytherapy) provided at the discretion of the ocular oncologist. The evaluation with examination under anesthesia, ultrasound biomicroscopy, and electroretinography (ERG) were performed before each injection to assess for tumor response and drug-related toxicity. A serious adverse event resulted in dose recalculation and ultimately early closure of the study. Regression pattern of vitreous disease and incidence of dose-limiting toxicities. Four patients were enrolled at an initial dose of 0.3 mg. Complete regression of vitreous seeds was noted in all patients after 5, 2, 2, and 1 injections (respectively). Two patients developed recurrent vitreous disease at 3 and 25 months after complete regression and ultimately required enucleation. A serious adverse event occurred in 1 patient who developed acute vision loss with extinguished ERG response 72 hours after the second injection; ultimately, this eye developed a cataract and required enucleation. After temporary suspension and dose modification, 3 patients were enrolled at an injection dose of 3 μg and treated with a total of 5, 2, and 1 injections, respectively. Complete regression of vitreous disease was not achieved in any patient though ERG amplitudes remained stable. After removal from protocol, all 3 patients had a complete response to intravitreal melphalan. Concern for dose escalation and further toxicity in the setting of an effective and safe alternative (melphalan) led to the termination of the study. Intravitreal carboplatin may be effective in treating progressive vitreous seeding at higher doses, but permanent retinal toxicity was observed. Other alternative agents should be considered. Proprietary or commercial disclosure may be found after the references.

The survival analysis and feasibility study of Pars Plana Vitrectomy (PPV) in the treatment of retinoblastoma.

To analyze the safety and efficacy of Pars Plana Vitrectomy (PPV) as a treatment for retinoblastoma patients and to evaluate the feasibility. We collected 342 eyes who had PPV after systemic chemotherapy in our retrospective study, then analyze the 5-year overall survival and 5-year event-free survival rate, recurrence rate, and metastasis rate. The above data were used to evaluate the feasibility of PPV in the treatment of retinoblastoma. The mean value of follow-up time was 62.9months from PPV. Of all 342 eyes, 18% eyes underwent enucleation of the eyeball. Excluding Non-PPV related deaths eyes, the 5-year overall survival rates and event-free survival were 95% and 80%; the tumor recurrence rate and metastasis rate were approximately 26% and 1.2%, respectively; the mortality was 3.9%. And the incidence of high-risk pathological factors of enucleated eyes after PPV was 32%. Our results suggest that Pars Plana Vitrectomy as a new approach to preserve the eyeball of RB children is feasible, especially for those patients who cannot be completely controlled by systemic chemotherapy or the tumors with vitreous seeds. Although the outcomes in our study are very optimistic, we also recommend an experienced eye surgeon to perform the operation and strictly control the indications for PPV surgery. And enough systemic chemotherapy is very important before and after surgery. Treatment study (Retrospective comparative study), III.

Complications of local treatment of retinoblastoma and their treatment (literature review)

Thanks to the treatments that are happening today, the survival rate of patients with retinoblastoma (Rb) has reached 100 %. Despite the positive results of Rb treatment, intraocular complications are observed in observations. Complications that cause visualization of the fundus impede the control of tumor tissue in dynamics, which is associated with enucleation of the eyeball. Despite modern advances in the use of intraocular surgery, a positive and important aspect is the fact that any experience of intraocular infections with a high risk of growth dissemination, which requires an accurate assessment of the state of growth in dynamics and confidence in the stability of remission, which is not always possible with opaque optical environments. In this regard, the question arises of conservative methods of treatment of persistent complications.Given the small age of patients, this makes it difficult to perform conservative treatment in full. Effective are retrobulbar injections, which deliver the drug as close as possible to the posterior pole of the eye. However, for the maximum concentration of the drug, frequent injections are necessary, which is quite traumatic, accompanied by pain, and their frequent implementation contributes to scarring of the retrobulbar tissue. One way to avoid these adverse events is retrobulbar infusion therapy.As a result of retrobulbar infusion therapy, a silicone tube (catheter) is placed in the retrobulbar space for several days, followed by the administration of drugs several times a day.The review contains data on intraocular complications after local treatment of Rb, as well as possible methods for their relief.

Ocular survival after intra-arterial chemotherapy for retinoblastoma improves with accrual of experience and programmatic evolution.

Intra-arterial chemotherapy (IAC) for the treatment of intraocular retinoblastoma has gained recognition as a method to improve ocular salvage; however, there is a paucity of evidence supporting treatment factors prognosticating ocular survival. All patients with retinoblastoma treated with IAC at a single institution between December 2008 and December 2019 were evaluated. Patient demographics, tumor classification, prior treatments, procedural data, other non-IAC therapies, adverse reactions, procedural complications, ocular outcomes, and overall survival were assessed via retrospective chart review. Factors suggestive of increased ocular survival were identified via univariate and multivariate analyses. The impact of accrued treatment experience was evaluated by grouping eyes by the respective year, IAC treatment was initiated. Forty-nine eyes of 43 patients were treated for retinoblastoma with IAC (256 total procedures). At least grade 3 neutropenia was observed following 19% of IAC procedures. The risk of neutropenia was not statistically different between single or multidrug IAC. Comparing those who received balloon-assisted intra-arterial chemotherapy (bIAC) in more than two-thirds of cycles to those who did not, the risk of arterial access site complications was not statistically different. Multivariate analysis revealed a significantly lower risk of enucleation associated with treatment era in years (hazard ratio [HR]=0.52-1.00, p<.05) and laser therapies (HR=0.02-0.60, p<.05). Ocular survival rates in patients treated with IAC for retinoblastoma at our institution have increased over time. Accrued treatment experience and programmatic changes have likely contributed. Larger, prospective series may lead to a better understanding of factors that consistently contribute to better ocular salvage.

Cryotherapy of retinoblastoma: 13-year experience

Introduction. Cryotherapy (CT) is one of the main methods of small retinoblastoma (Rb) treatment and remains the “gold standard” for the treatment of small tumors of pre-equatorial localization, however, the number of studies in the literature on this problem is small, and they are represented only by single studies.Purpose of the study – to evaluate long-term results of CT of Rb.Materials and methods. During the period from 2008 to 2021 CT was performed in 87 children (98 eyes, 169 tumors) with Rb. 49 (56 %) patients were boys, 38 (44 %) were girls. The average age at the time of treatment was 22 months (from 0 to 73 months). Bilateral RB was observed in 70 (80 %) patients, unilateral – in 17 (20 %). In 19 (22 %) cases, CT was performed on a single eye. A total of 169 tumors were treated by CT. Most of the treated tumors (138 foci, 82 %) had pre-equatorial localization (35 tumors – on the mid periphery and 103 tumors – on the far periphery of the fundus). 31 (18 %) tumors located postequatorially. The mean tumor thickness was 1.2 (from 0.4 to 2.9) mm, the mean basal diameter was 2.2 (from 0.9 to 4.9) mm.In the vast majority of cases (n = 78, 87 %), CT was performed with an incision of the conjunctiva and separation of the tenon capsule in the projection of the tumor, then a double application with an exposure of 60 seconds was carried out according to the “classic” technology (“freeze–thaw”). In 13 % of cases (n = 9), CT was performed transconjunctivally without a conjunctival incision. In all cases, carbon dioxide (–78 ºC) was used as a refrigerant.Results. Complete tumor regression after CT was achieved in 63 % of cases (106 tumors), of which in 91 % of cases (96 tumors) – after one CT session, in 8 % (9 tumors) – after 2 sessions, in one (1 %) case– after 4 CT sessions. In 10 % of cases (17 tumors) an incomplete regression was observed and subsequent transpupillary laser thermotherapy was performed. In 27 % of cases (43 tumors), continued tumor growth or recurrence of the tumor was detected, and therefore other methods of local treatment were used (brachytherapy, laser thermotherapy, intra-arterial and intravitreal chemotherapy). As a result of organ-preserving treatment, 90 (92 %) eyes were preserved, 8 (8 %) eyes were enucleated.Complications after CT included vitreous hemorrhage in 3 (3 %) patients, preretinal hemorrhage in 7 (8 %) cases, subretinal hemorrhage in 2 %, local retinal detachment in 2 %, one (1 %) case of retinal tear, and vitreoretinal traction in 2 (2 %) patients. The mean follow-up time after CT was 44 months (from 4 to 121 months).Conclusion. CT still takes an important place in Rb local treatment, especially in the treatment of small tumors of peripheral localization. However, long-term results have shown that one session of CT is often not enough to achieve complete tumor regression and it requires either repeated use of CT or application of other local methods, mostly transpupillary laser thermotherapy. However, the use of CT is especially relevant in the treatment of small tumors of pre-equatorial localization, which are resistant to thermotherapy, especially in cases of a tumor height more than 1 mm and basal diameter more than 2 mm, which are too large and inconvenient for thermotherapy of peripheral Rb.

Highly Efficient Photodynamic Therapy with Mitochondria-Targeting Aggregation-Induced Emission Photosensitizer for Retinoblastoma.

Retinoblastoma (RB) is an aggressive eye cancer in infancy and childhood, lethal by metastasis if left untreated. Currently, the survival rate and the chance of saving vision depend on the severity of the disease. In this work, a highly efficient photodynamic ophthalmic therapy for RB is reported by employing an isoquinolinium-based aggregation-induced-emission (AIE) photosensitizer (PS) TPE-IQ-2O for photodynamic inactivation (PDI). TPE-IQ-2O is an efficient mitochondria-targeting photosensitizer as an efficient guided photodynamic therapy (PDT) agent against cancer cells. Maximizing cancer-selectively damage to tumors with minimized side effects on normal tissue is essential for effective anticancer PDT and provides long-lasting protection against metastasis. In addition, TPE-IQ-2O can effectively reduce the degree of tissue inflammation by inhibiting the expression of related inflammatory factors. TPE-IQ-2O also exhibits excellent biocompatibility with a neglectable hemolysis effect on mouse red blood cells and almost no killing effect on mammalian cells, which enables its potential applications in the treatment of RB.

Epidemiological and Clinical Presentation of Retinoblastoma among Nepalese Children in 2019.

Suresh B.K. RasailyObjectives Retinoblastoma (RB) is rare but potentially fatal if left untreated. This study aimed to evaluate the epidemiological profile, clinical manifestation, classification, and affordability of RB treatment among Nepalese children in the year 2019. Materials and Method A multicentric, multiethnic hospital-based cross-sectional study after ethical approval from the National Health Research Council was conducted from January 2019 to December 2019 by incorporating ophthalmologists all over the nation. Twenty-seven RB centers were selected. All the RB presented in the RB centers either newly diagnosed or ongoing treatment consented to the study were included and failed to consent for the study, RB survivors were excluded from the study. Data based on demographic profile, clinical manifestation, ethnical and geographical distribution, and treatment received were collected in the customized Google Form. Each case was classified at the time of diagnosis as per the International Classification of Retinoblastoma groups and different treatment modalities offered as per grouping and staging. The affordability of treatment was calculated using a catastrophic approach. Statistical Analysis Data were entered into Microsoft Excel 2010 and analyzed using Statistical Package for Social Sciences version 20. Result A total of 34 RB cases, 21 (61.76%) in ongoing treatment group and 13 (38.2%) in newly diagnosed group presented in the RB centers. Out of total, 32 (64.7%) had unilateral and 12 (35.3%) cases had bilateral involvement. The majority of patients was from Province 1 (35.3%) and belonged to the upper caste (38.2%). Leukocoria was the most common presentation (73.9%) followed by proptosis, red eye, and phthisis bulbi. More than 75% patients presented at advanced group D (54%) and E (21%) and stage 0 (90%). More than 90% of patients received systemic chemotherapy, and 42.6% received transpupillary thermotherapy. The average cost of RB treatment was estimated to be 521% of the nonfood expense of the family which is unaffordable to almost all cases (100%). Conclusion Leukocoria is the most common mode of clinical presentation in both unilateral and bilateral RBs. Early diagnosis and appropriate treatment are key to success for saving life, sight, and eye. However, community awareness programs against RB, active referral networks, and the establishment of chemotherapy centers with trained human resources are needed to reduce loss of life, sight, and eye.

Bioinformatics Analysis and Experimental Identification of Immune-Related Genes and Immune Cells in the Progression of Retinoblastoma.

Retinoblastoma (RB) is the most common type of aggressive intraocular malignancy in children. The alteration of immunity during RB progression and invasion has not yet been well defined. This study investigated significantly altered immune-associated genes and cells related to RB invasion. The differentially expressed immune-related genes (IRGs) in noninvasive RB and invasive RB were identified by analysis of two microarray datasets (GSE97508 and GSE110811). Hub IRGs were further identified by real time PCR. The single-sample gene set enrichment analysis algorithm and Pearson correlation analysis were used to define immune cell infiltration and the relationships between hub IRGs and immune cells. Cell viability and migration were evaluated by CCK-8 and Transwell assays. A xenograft mouse model was used to verify the relationship between Src homology 3 (SH3) domain GRB2-like 2 (SH3GL2) expression and myeloid-derived suppressor cells (MDSCs). Eight upregulated genes and six downregulated IRGs were identified in invasive RB. Seven IRGs were confirmed by real-time PCR. Moreover, the proportions of MDSCs were higher in invasive RB tissues than in noninvasive RB tissues. Furthermore, correlation analysis of altered immune genes and cells suggested that SH3GL2, Langerhans cell protein 1 (LCP1) and transmembrane immune signaling adaptor TYROBP have strong connections with MDSCs. Specifically, decreased SH3GL2 expression promoted the migration of RB cells in vitro, increased the tumor size and weight, and increased the numbers of MDSCs in the tumor and spleen in vivo. This study indicated that SH3GL2 and MDSCs play a critical role in RB progression and invasion and provide candidate targets for the treatment of RB.

MDM2 inhibitors-mediated disruption of mitochondrial metabolism: A novel therapeutic strategy for retinoblastoma

MDM2 is the principal inhibitor of p53, and MDM2 inhibitors can disrupt the physical interaction between MDM2 and p53. The half-life of p53 is very short in normal cells and tissues, and an uncontrolled increase in p53 levels has potential harmful effects. It has been shown that p53 is frequently mutated in most cancers; however, p53 mutations are rare in retinoblastoma. Therefore, therapeutic strategies aimed at increasing the expression levels of wild-type p53 are attractive. In this minireview, we discuss the potential use of nutlin-3, the prototype small molecule inhibitor that disrupts the MDM2-p53 interaction, for the treatment of retinoblastoma. Although p53 has pleiotropic biological effects, the functions of p53 depend on its sub-cellular localization. In the nucleus, p53 induces the transcription of a vast array of genes, while in mitochondria, p53 regulates mitochondrial metabolism. This review also discusses the relative contribution of p53-mediated gene transcription and mitochondrial perturbation for retinoblastoma treatment.